1. DuraSealTM Dural Sealant System PMA P040034

2. Presenters Vice President, Clinical, Regulatory, and Quality
Eric Ankerud, J.D. – Confluent Surgical, Inc.
Vice President, Clinical, Regulatory, and Quality
Patrick Campbell, Ph.D. – Confluent Surgical, Inc.
Vice President, Research & Development
John Tew, M.D. – Mayfield Clinic
Professor, Department of Neurosurgery, University of Cincinnati
G. Rees Cosgrove, M.D. – Massachusetts General Hospital
Associate Professor of Surgery, Harvard Medical School
Harry van Loveren, M.D. –Tampa General Hospital
Professor and Chairman, Director of Skull Base and Cerebrovascular Surgery, University of South Florida

3. Presentation Overview
Project Overview – Eric Ankerud, J.D.
Technology Overview – Pat Campbell, Ph.D.
Project Rationale – John Tew, M.D.
US Pivotal Trial Results – G. Rees Cosgrove, M.D.
Safety Evaluation – Harry van Loveren, M.D.

4. Company Overview
Mission: Development of in-situ polymerized biomaterials to address the unmet needs of surgical wound healing including surgical tissue sealing, post surgical adhesion prevention, and hemostasis
Founded: 1998
People: 30 employees
Facility: Waltham, Massachusetts
Products: Commercially available OUS

5. DuraSeal Dural Sealant System
Thumb piece
Syringes (2)
Sprayer
Components
Powder Vial

6. Pre-Clinical Summary
DuraSeal is non-toxic and safe, up to 40X human dose
DuraSeal is not neurotoxic, and allows complete neodura formation
Intraoperative and postoperative sealing efficacy demonstrated in relevant canine model
Ability to image DuraSeal has been demonstrated, and has complete absorption over 8 weeks

7. “Water Tight” Closure Remains Elusive
Achieving “water tight” closure is basic tenet of neurosurgical practice
Controlling intraoperative leakage is important to prevent CSF leakage and development of postoperative complications:
Suture pinholes and space between sutures act as “one-way” valve for CSF leakage
Subdural collections of CSF fluid may develop into pseudomeningoceles and overt incisional leaks with potential for serious post-operative sequelae
Suture pinholes and space between sutures act as “one-way” valve for CSF leakage
Subdural collections of CSF fluid may develop into pseudomeningoceles and overt incisional leaks with potential for serious post-operative sequelae

8. CSF Leak Causes Postoperative Morbidity
Meningitis – may lead to delayed neurologic complications
Prolonged hospitalization and increased patient cost
Interference with wound healing (dehiscence)
Abscess formation
Additional surgical intervention often required
Speak to placement of lumbar drains and LP shunts as surgical interventions taken.
Find reference for cost of CSF leak
Risk factor for development of meningitis/abscess (relative risk 16.0) Korinek et al.
Meningitis most frequent and severe complication and is associated with high mortality rate (1-20%) Shaffrey et al.

9. Methods For Sealing Sutured Dural Closure
Current Methods
FDA-Approved Devices
Products Used Off Label
None
NO STANDARD OF CARE
Fibrin Sealant (e.g. Tisseel)
Absorbable gelatin (e.g. Gelfoam)
Collagen hemostatic agents (e.g. Surgicel)
Other bioadhesives (e.g. BioGlue)
Dr. Tew to speak to the fact that none of the products listed actually work for dural sealing.
Speaking points – BioGlue toxicity
Integra’s products

10. US Pivotal Study Objective
To evaluate the safety and effectiveness of the DuraSeal Dural Sealant System as an adjunct to sutured dural repair during cranial surgery to provide watertight closure

11. Study Design Prospective Multi-center Non-randomized, single arm study
11 participating sites
10 United States
1 Europe

12. Follow-up Compliance Patients Enrolled n=132
Intra-operative Screen Failures
n=21
Patients Treated with DuraSeal
n=111
Immediate Post-operative Visit
(within 7 days of surgery)
n=111
100% of patients evaluated
Patient Death
n=1 at 27 days
Post-op
6 Week Visit
n=110
99% of patients evaluated
Patient Death
n=1 at 85 days
Post-op
Lost to
Follow-up
n=2
3 Month Visit
n=107
98% of patients evaluated

13. Primary Efficacy Analysis-Intraoperative Sealing Success
Results
Intent To Treat*
(includes 2 non-evaluable patients)
98.2% (109*/111)
[95% CI: ]
Per Protocol
(includes all evaluable patients)
100% (109/109)
[95% CI: ]
* Two patients had no leak after Valsalva maneuver, but pressure reached was only to 10 cm H2O and, therefore, were not evaluable

14. Summary Primary efficacy endpoint was met
Adverse events consistent in nature, frequency and severity for patients undergoing cranial surgery

15. Conclusion
In the patient population evaluated, the benefits associated with the use of the DuraSeal Sealant outweigh any potential risks associated with the use of the device